Association between ethylene oxide exposure and osteoarthritis risk mediated by oxidative stress: evidence from NHANES 2013–2020

Xinyue Yang, Jianwen Wang, Chengcheng Wei, Jia Tian, Lizhao Yan, Qishun Huang

¹Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China²Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

Abstract

Ethylene oxide is extensively used for sterilizing medical equipment, and its carcinogenicity has been well documented. Furthermore, the onset of multiple diseases, including diabetes and hypertension, has been demonstrated to be associated with exposure to this compound. However, its association with osteoarthritis risk remains elusive. The study analyzed data from the National Health and Nutrition Examination Survey from 2013–2020, which included 6088 American adults, among whom 763 (12.5%) were diagnosed with osteoarthritis. We utilized a weighted generalized linear model to assess the correlation between ethylene oxide exposure levels and osteoarthritis risk. This study used mediation analysis to assess the functions of indicators of oxidative stress (γ-glutamyl transferase) and inflammation (alkaline phosphatase, white blood cell count, neutrophil count, and lymphocyte count) as mediators of how ethylene oxide affects osteoarthritis. The analysis revealed that elevated levels of ethylene oxide were correlated with a higher risk of osteoarthritis, even when controlling for other variables. The odds of developing osteoarthritis were 1.86 times higher in the fourth quartile than in the first quartile (95% confidence interval: 1.20–2.88, P = 0.0097, P for trend = 0.0087). Subgroup analyses indicated consistency across different cohorts. Mediation analysis revealed that oxidative stress (γ-glutamyl transferase), not inflammation, was the mediator linking ethylene oxide levels to the risk of osteoarthritis. This finding in a sample of American adults revealed a direct relationship between exposure to ethylene oxide and increased osteoarthritis risk. Oxidative stress has been suggested as a possible biological explanation for osteoarthritis caused by ethylene oxide.

摘要：环氧乙烷广泛用于医疗设备的灭菌，其致癌性已被充分证明。此外，包括糖尿病和高血压在内的多种疾病的发病已被证明与接触这种化合物有关。然而，它与骨关节炎风险的关系仍然难以捉摸。该研究分析了2013-2020年全国健康与营养检查调查的数据，其中包括6088名美国成年人，其中763人（12.5%）被诊断患有骨关节炎。我们使用加权广义线性模型来评估环氧乙烷暴露水平与骨关节炎风险之间的相关性。本研究采用中介分析评估氧化应激指标（γ-谷氨酰转移酶）和炎症指标（碱性磷酸酶、白细胞计数、中性粒细胞计数和淋巴细胞计数）作为环氧乙烷影响骨关节炎的介质的功能。分析显示，即使在控制其他变量的情况下，环氧乙烷水平的升高也与骨关节炎的高风险相关。第四个四分位数患骨关节炎的几率是第一个四分位数的1.86倍（95%置信区间：1.20-2.88,P = 0.0097， P为趋势值= 0.0087）。亚组分析显示了不同队列的一致性。中介分析显示氧化应激（γ-谷氨酰转移酶），而不是炎症，是连接环氧乙烷水平与骨关节炎风险的中介。这一发现在美国成年人样本中揭示了暴露于环氧乙烷和骨关节炎风险增加之间的直接关系。氧化应激已被认为是环氧乙烷引起的骨关节炎的可能生物学解释。